Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib

Titre officiel

A Phase II Study Assessing the Efficacy of Osimertinib in Combination With Savolitinib in Patients With EGFRm+ and MET+, Locally Advanced or Metastatic Non Small Cell Lung Cancer Who Have Progressed Following Treatment With Osimertinib.

Sommaire:

This study (the SAVANNAH study) will investigate the efficacy of osimertinib in combination with savolitinib in patients with EGFRm+ and MET+, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib

Description de l'essai

Primary Outcome:

• Objective response rate (ORR) by investigator assessment in accordance with RECIST 1.1
• Objective response rate (ORR) by investigator assessment in accordance with RECIST 1.1

Secondary Outcome:

• Duration of Response (DoR) by investigator assessment in accordance with RECIST 1.1.
• Progression-free survival (PFS) by investigator assessment in accordance with RECIST 1.1.
• Overall Survival (OS) by all cause mortality.
• Objective response rate (ORR) by investigator assessment in accordance with RECIST 1.1.
• Objective response rate (ORR) by investigator assessment in accordance with RECIST 1.1.
• Duration of Response (DoR) by investigator assessment in accordance with RECIST 1.1.
• Progression-free survival (PFS) by investigator assessment in accordance with RECIST 1.1.
• Overall Survival (OS) by all cause mortality.
• Objective response rate (ORR) by investigator assessment in accordance with RECIST 1.1.
• Duration of Response (DoR) by investigator assessment in accordance with RECIST 1.1.
• Progression-free survival (PFS) by investigator assessment in accordance with RECIST 1.1.
• Overall Survival (OS) by all cause mortality.
• Objective response rate (ORR) by investigator assessment in accordance with RECIST 1.1.
• Duration of Response (DoR) by investigator assessment in accordance with RECIST 1.1.
• Progression-free survival (PFS) by investigator assessment in accordance with RECIST 1.1.
• Overall Survival (OS) by all cause mortality.
• Objective response rate (ORR) assessed by BICR in accordance with RECIST 1.1
• Duration of Response (DoR) assessed by BICR in accordance with RECIST 1.1
• Progression-free survival (PFS) assessed by BICR in accordance with RECIST 1.1
• Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality-of-life questionnaire (QLQ-C30).
• Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) complementary 13-item quality-of-life questionnaire - lung cancer symptoms questionnaire (QLQ-LC13).
• Plasma concentrations of osimertinib, savolitinib and their metabolites.
• Total clearance in EGFR mutations at 6-weeks after therapy initiation (percentage and absolute change from baseline in EGFR mutation allele frequencies).
• AEs, SAEs and discontinuation rate due to AEs, as characterized and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5.

The combination of osimertinib with savolitinib in this study (the SAVANNAH study) will explore if the combination will overcome MET-amplification as a mechanism of resistance. The SAVANNAH study will investigate the efficacy of osimertinib in combination with savolitinib in patients with EGFRm+ and MET-amplified/overexpressed, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib. Eligible patients will be those with histologically or cytologically confirmed diagnosis of EGFRm+, MET amplified/overexpressed (FISH10+ and/or IHC90+) NSCLC that is locally advanced or metastatic and is not amenable to further surgery or radiation therapy with curative intent. The disease must have progressed following treatment with first line osimertinib. Patients must have confirmation of MET-amplified/overexpressed tumour by central FISH and IHC testing (requirements summarised in the main body of the protocol and fully explained in the Central Laboratory Manual). Patients must not have received prior or current treatment with savolitinib or another MET inhibitor. All patients confirmed as eligible will begin treatment on Day 1 with osimertinib + savolitinib combination therapy or placebo to osimertinib + savolitinib. Treatment will continue in 28 day cycles until either objective disease progression by investigator per RECIST 1.1 is assessed, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.

Voir cet essai sur ClinicalTrials.gov